Orbitofrontal Cortex and Cognitive-Motivational Impairments in Psychostimulant Addiction

Evidence from Experiments in the Non-human Primate

Authors

  • PETER OLAUSSON,

    1. Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, Connecticut, USA
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  • J. DAVID JENTSCH,

    1. Department of Psychology, UCLA, Los Angeles, California, USA
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  • DILJA D. KRUEGER,

    1. Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, Connecticut, USA
    2. The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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  • NATALIE C. TRONSON,

    1. Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, Connecticut, USA
    2. Department of Psychiatry & Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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  • ANGUS C. NAIRN,

    1. Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, Connecticut, USA
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  • JANE R. TAYLOR

    1. Department of Psychiatry, Division of Molecular Psychiatry, Yale University, New Haven, Connecticut, USA
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Address for correspondence: Department of Psychiatry, Division of Molecular Psychiatry, Yale University, CMHC, 34 Park St, New Haven, CT 06508. Voice: (203) 974 7752; fax: (203) 974 7897.
 peter.olausson@yale.edu

Abstract

Abstract:Addiction is characterized by compulsive drug use despite adverse consequences. The precise psychobiological changes that underlie the progression from casual use to loss of control over drug-seeking and drug-taking behavior are not well understood. Here we report that short-term cocaine exposure in monkeys is sufficient to produce both selective deficits in cognitive functions dependent on the orbitofrontal cortex (OFC) concurrent with enhancements in motivational processes involving limbic-striatal regions. Additional findings from behavioral studies and analyses of the synaptic proteome provide new behavioral and biochemical evidence that cocaine-induced neuroadaptations in cortical and subcortical brain regions result in dysfunctional decision-making abilities and loss of impulse control that in combination with enhancements of incentive motivation may contribute to the development of compulsive behavior in addiction.

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